Cofilin Determines the Migration Behavior and Turning Frequency of Metastatic Cancer Cells

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2007 Nov 21

PMID 18025308

Citations 107

Authors

Mazen Sidani

Deborah Wessels

Ghassan Mouneimne

Mousumi Ghosh

Sumanta Goswami

Corina Sarmiento

Weigang Wang

Spencer Kuhl

Mirvat El-Sibai

Jonathan M Backer

Robert Eddy

David Soll

John Condeelis

Affiliations

Soon will be listed here.

Abstract

We have investigated the effects of inhibiting the expression of cofilin to understand its role in protrusion dynamics in metastatic tumor cells, in particular. We show that the suppression of cofilin expression in MTLn3 cells (an apolar randomly moving amoeboid metastatic tumor cell) caused them to extend protrusions from only one pole, elongate, and move rectilinearly. This remarkable transformation was correlated with slower extension of fewer, more stable lamellipodia leading to a reduced turning frequency. Hence, the loss of cofilin caused an amoeboid tumor cell to assume a mesenchymal-type mode of movement. These phenotypes were correlated with the loss of uniform chemotactic sensitivity of the cell surface to EGF stimulation, demonstrating that to chemotax efficiently, a cell must be able to respond to chemotactic stimulation at any region on its surface. The changes in cell shape, directional migration, and turning frequency were related to the re-localization of Arp2/3 complex to one pole of the cell upon suppression of cofilin expression.

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